tbuckley/cabot-search huggingface dataset:
Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment
Authors: Changwei Li, Yang Pan, Ruiyuan Zhang, Zhijie Huang, Davey Li, Yunan Han, Claire Larkin, Varun Rao, Xiao Sun, Tanika N. Kelly
Journal: Circulation Research (2023)

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which is determined at zygote formation, is among the earliest risk factors for CVD. With major advances in molecular technology, including the emergence of gene-editing techniques, along with deep whole-genome sequencing and high-throughput array-based genotyping, scientists now have the opportunity to not only discover genomic mechanisms underlying CVD but use this knowledge for the life-course prevention and treatment of these conditions. The current review focuses on innovations in the field of genomics and their applications to monogenic and polygenic CVD prevention and treatment. With respect to monogenic CVD, we discuss how the emergence of whole-genome sequencing technology has accelerated the discovery of disease-causing variants, allowing comprehensive screening and early, aggressive CVD mitigation strategies in patients and their families. We further describe advances in gene editing technology, which might soon make possible cures for CVD conditions once thought untreatable. In relation to polygenic CVD, we focus on recent innovations that leverage findings of genome-wide association studies to identify druggable gene targets and develop predictive genomic models of disease, which are already facilitating breakthroughs in the life-course treatment and prevention of CVD. Gaps in current research and future directions of genomics studies are also discussed. In aggregate, we hope to underline the value of leveraging genomics and broader multiomics information for characterizing CVD conditions, work which promises to expand precision approaches for the life-course prevention and treatment of CVD.
Distant antimetastatic effect of enterotropic colon cancer–derived α4β7 <sup>+</sup> CD8 <sup>+</sup> T cells
Authors: Virginie Feliu, Carlos Gomez-Roca, Marie Michelas, Noémie Thébault, Françoise Lauzéral-Vizcaino, Anna Salvioni, Lise Scandella, Emeline Sarot, Carine Valle, Camille-Charlotte Balança, Clara-Maria Scarlata, Jean-Pierre Delord, Maha Ayyoub, Christel Devaud
Journal: Science Immunology (2023)

Despite the high prognostic value of immune infiltrates in colorectal cancer (CRC), metastatic disease remains resistant to immunotherapy by immune checkpoint blockade (ICB). Here, we show, in metastatic CRC preclinical models, that orthotopically implanted primary colon tumors exert a colon-specific antimetastatic effect on distant hepatic lesions. Enterotropic α4β7 integrin–expressing neoantigen-specific CD8 T cells were key components of the antimetastatic effect. Accordingly, the presence of concomitant colon tumors improved control of liver lesions by anti–PD-L1 proof-of-concept immunotherapy and generated protective immune memory, whereas partial depletion of α4β7 + cells abrogated control of metastases. Last, in patients with metastatic CRC, response to ICB was associated with expression of α4β7 integrin in metastases and with circulating α4β7 + CD8 T cells. Our findings identify a systemic cancer immunosurveillance role for gut-primed tumor-specific α4β7 + CD8 T cells.
Air Pollution, Built Environment, and Early Cardiovascular Disease
Authors: Kai Zhang, Robert D. Brook, Yuanfei Li, Sanjay Rajagopalan, Juyong Brian Kim
Journal: Circulation Research (2023)

As the world's population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related risk factors. While epidemiological studies have examined the role of a few environmental factors with early cardiovascular disease, the relationship with the broader environment remains poorly defined. In this article, we provide a brief overview of studies that have examined the impact of the environment including the built physical environment, discuss current challenges in the field, and suggest potential directions for future research. Additionally, we highlight the clinical implications of these findings and propose multilevel interventions to promote cardiovascular health among children and young adults.
Imaging Early Life Cardiovascular Phenotype
Authors: Vinithra Varadarajan, Samuel S. Gidding, Colin Wu, J. Jeffrey Carr, Joao A.C. Lima
Journal: Circulation Research (2023)

The growing epidemics of obesity, hypertension, and diabetes, in addition to worsening environmental factors such as air pollution, water scarcity, and climate change, have fueled the continuously increasing prevalence of cardiovascular diseases (CVDs). This has caused a markedly increasing burden of CVDs that includes mortality and morbidity worldwide. Identification of subclinical CVD before overt symptoms can lead to earlier deployment of preventative pharmacological and nonpharmacologic strategies. In this regard, noninvasive imaging techniques play a significant role in identifying early CVD phenotypes. An armamentarium of imaging techniques including vascular ultrasound, echocardiography, magnetic resonance imaging, computed tomography, noninvasive computed tomography angiography, positron emission tomography, and nuclear imaging, with intrinsic strengths and limitations can be utilized to delineate incipient CVD for both clinical and research purposes. In this article, we review the various imaging modalities used for the evaluation, characterization, and quantification of early subclinical cardiovascular diseases.
Life Course Cardiovascular Health: Risk Factors, Outcomes, and Interventions
Authors: Havisha Pedamallu, Rachel Zmora, Amanda M. Perak, Norrina B. Allen
Journal: Circulation Research (2023)

Since it was first defined by the American Heart Association in 2010, cardiovascular health (CVH) has been extensively studied across the life course. In this review, we present the current literature examining early life predictors of CVH, the later life outcomes of child CVH, and the relatively few interventions which have specifically addressed how to preserve and promote CVH across populations. We find that research on CVH has demonstrated that prenatal and childhood exposures are consistently associated with CVH trajectories from childhood through adulthood. CVH measured at any point in life is strongly predictive of future cardiovascular disease, dementia, cancer, and mortality as well as a variety of other health outcomes. This speaks to the importance of intervening early to prevent the loss of optimal CVH and the accumulation of cardiovascular risk. Interventions to improve CVH are not common but those that have been published most often address multiple modifiable risk factors among individuals within the community. Relatively few interventions have been focused on improving the construct of CVH in children. Future research is needed that will be both effective, scalable, and sustainable. Technology including digital platforms as well as implementation science will play key roles in achieving this vision. In addition, community engagement at all stages of this research is critical. Lastly, prevention strategies that are tailored to the individual and their context may help us achieve the promise of personalized prevention and help promote ideal CVH in childhood and across the life course.
AB0604 IDENTIFYING THE RISK FACTORS AND INCREASING MORTALITY OF PULMONARY ARTERIAL HYPERTENSION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Y. F. Fang, Y. F. Chen
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Patients with systemic lupus erythematosus (SLE) have a risk of pulmonary arterial hypertension (PAH), which could be fatal. <h3>Objectives</h3> The goal of this study was to identify the risk factors for mortality in patients with PAH. <h3>Methods</h3> Patients with SLE treated at Chang Gung Memorial Hospital were included in this retrospective cohort study. Univariate and multivariate COX regression, as well as Kaplan–Meier survival curve analysis were conducted to investigate risks in SLE patients. <h3>Results</h3> The average age at diagnosis was 40.78 ± 15.92 years. A total of 42 (6.1%) of the 689 patients had PAH. Patients with PAH exhibited shorter follow-up duration, higher disease activities, higher incidence rates of comorbidities patients without PAH. Physicians preferred to use more Cyclophosphamide and less hydroxychloroquine in PAH patients. Cox regression adjusted analysis indicated that PAH (hazard ratio = 2.709, 95% CI = 1.631, 4.499, <i>p</i> &lt;0.001), old age at diagnosis (HR = 1.057, 95% CI = 1.045, 1.070, <i>p</i> &lt; 0.001), high SLEDAI score (HR = 1.074, 95% CI = 1.040, 1.109, <i>p</i> &lt; 0.001), end-stage kidney disease (ESKD) (HR = 2.533, 95% CI = 1.620, 3.961, <i>p</i> &lt; 0.001) and Cyclophosphamide treatment (HR = 1.687, 95% CI = 1.058, 2.689, <i>p</i> &lt; 0.028) were all linked to increased mortality. Moreover, the Kaplan–Meier survival curve analysis revealed that patients with pericarditis had a higher mortality rate (log-rank test, <i>p</i> &lt; 0.001). <h3>Conclusion</h3> A 6.1% proportion of SLE patients have manifestations of PAH. Moreover, SLE patients with PAH have a greater risk of mortality. Therefore, these patients need intense screening and treatment of PAH. <h3>References: Nil.</h3> <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0264 PREDICTION OF FLARE FOLLOWING GLUCOCORTICOIDS WITHDRAWAL IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING CSDMARDS: A REAL-LIFE STUDY
Authors: W. Xie, Z. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> In patients with rheumatoid arthritis (RA), glucocorticoids (GC) should be firstly discontinued before considering tapering conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) or other biological agents. <h3>Objectives</h3> We aim to determine risk factors for flare after GC withdrawal in RA patients undergoing csDMARDs. <h3>Methods</h3> Electronic database searches of PubMed, EMBASE and Cochrane Library were performed. Observational studies that assessed the association of dementia with DMARDs in RA were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were used as summary statistic, with either fixed-effects or random-effects model. The certainty of evidence using the GRADE system. <h3>Results</h3> In total, 115 RA patients discounted GC in the context of csDMARDs (methotrexate: 80%; hydroxychloroquine: 61%; csDMARDs combination: 79%). Of these, twenty-four patients experienced flare after GC discontinuation. Compared with relapse-free patients, flare patients were more likely to have established RA (75% vs. 49%, p=0.025), higher median cumulative prednisolone dosages (3.3g vs. 2.2g, p=0.004), and higher proportion of dissatisfied RA control during GC usage (66% vs. 33%, p=0.038). In multivariate analysis, significantly increased flare risk was predicted by established RA (OR 2.93 [1.02-8.43]), cumulative prednisolone doses&gt;2.5g (OR 3.69 [1.34-10.19]) and dissatisfied RA control (OR 3.00 [1.09-8.30]). <h3>Conclusion</h3> Flare following GC withdrawal is not common in RA patient undergoing csDMARDs therapy. Established RA, higher cumulative GC doses and dissatisfied RA control before GC discontinuation are important factors associated with flare after GC withdrawal. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB0006 CLINICAL, BIOLOGICAL AND GENETIC BIOMARKERS ASSOCIATED WITH DIFFERENT PHENOTYPES OF SYSTEMIC LUPUS ERYTHREMATOSUS IN PARAGUAYAN PATIENTS
Authors: I. Acosta Colmán, Z. Morel, A. Ayala-Lugo, V. Jolly, I. De Guillén, P. Langjahr, M. Vázquez, C. Holt, A. Paats, M. Martínez, M. E. Acosta
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by a very heterogeneous clinical picture that makes diagnosis and follow-up of these patients difficult. <h3>Objectives</h3> Identify correlations between clinical, immunological and genetic biomarkers with clinical manifestations in SLE in Paraguayan patients. <h3>Methods</h3> Retrospective study of data from medical records and immunological and genetic studies of patients with SLE from Paraguay. A descriptive analysis was performed based on the type of variable. HLA allele frequency (DPA1, DPB1, DQA1, DQB1, and DRB1) was calculated and univariate logistic regression analysis was performed between each of the explanatory variables and the presence/absence of each of the phenotypes. The odds ratio. (OR), the 95% confidence interval (95%CI), and the p-value were recorded. Associations with a p-value less than 0.05 were considered statistically significant associations. <h3>Results</h3> 104 patients with SLE were included, 86% female with a mean age value of 32.80 ±10.36 years. An association was identified between anti-dsDNA and the presence of the renal phenotype and anti-dsDNA with the absence of the joint and hematological phenotype. The IgM isotype RF was associated with the absence of the renal phenotype. HLA DQB1* 02:02 and HLA DRB1* 07:01 associated with cutaneous phenotype were identified. An association was identified between the age of onset of the disease and the presence of the joint phenotype. No other associations were identified with the other variables studied. <h3>Conclusion</h3> possible clinical, immunological and genetic biomarkers of phenotypes have been identified in patients with SLE of Paraguayan origin. <h3>References</h3> [1]Takvorian S.U, Merola J.F., Costenbader K.H. Cigarette smoking, alcohol consumption and risk of systemic lupus erythematosus Lupus. 2014; 537-544. [2]Barbhaiya M., Tedeschi S.K., Malspeis B., Lu S., Kreps D., Sparks, J.A. et al. Cigarette smoking and the risk of systemic lupus erythematosus, overall and by anti-double stranded DNA antibody subtype, in the Nurses' Health Study cohorts. Ann Rheum. 2018; 196-202. [3]Barbhaiya M, Lu B, Sparks JA, et al. Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts. Arthritis Care Res (Hoboken). 2017;69(3):384-392. [4]Williams JN, Chang SC, Sinnette C, Malspeis S, Parks CG, Karlson EW, et al. Pesticide exposure and risk of systemic lupus erythematosus in an urban population of predominantly African-American women. Lupus. 2018;27(13):2129-2134. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
Prevalence and Clinical Outcome of Omicron Breakthrough Infection in Patients With Hematologic Disease: A Prospective Observational Cohort Study
Authors: Kentaro Narita, Daisuke Ikeda, Mizuki Seki, Ami Fukumoto, Rikako Tabata, Yuka Uesugi, Daisuke Miura, Masami Takeuchi, Masahiro Doi, Yuka Umezawa, Yoshihito Otsuka, Kosei Matsue
Journal: HemaSphere (2023)
AB1838-HPR THE TYPE AND THE EFFECT OF PHYSICAL ACTIVITY ON QUALITY OF LIFE AND FATIQUE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN GREECE: A CROSS-SECTIONAL STUDY
Authors: D. Bonia
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic Lupus Erythematosus (SLE) is an autoimmune disease with sever symptoms, such as fatigue and has a high impact on patient's quality of life. <h3>Objectives</h3> The aim of this study was to determine the rate, the type, and the effect of physical activity (P.A.), and exercise in patients with SLE on quality of life and fatigue in Greece. <h3>Methods</h3> Three questionnaires were used to measure quality of life (SF-36), fatigue (FSS), and P.A. (mIPAQ). 101 patients with SLE from Greece answered about their personal choices. For statistics the IBM SPSS 25 was used for the statistical analysis. Descriptive analysis conducted to describe quantitative variables of interests. Data normality was verified from Kolmogorov-Smirnov test, and Pearson Correlation test was performed to determine the relationship between P.A. and QoL and Fatigue. <h3>Results</h3> The results showed that the sample average for QoL was 48.3(±19,3), for Fatigue 41,73(±7,2). The total score of P.A. was 1603,79(±1695.8) METs. Furthermore, for vigorous P.A. was 557,79(±987,6) METs, for moderate P.A. 824,65(±811,6) METs, and for low P.A. 239,87(±405) METs. The most common type of P.A. was housekeeping and cleaning for 74% of the sample, and even thought it is not considered as P.A. activity there was an option. A high average (50,5%) of the sample was presented by patients who chose to remain seated during the day. Positive correlation between P.A. and QoL was found (R=,385, P&lt;,01). Negative correlation between P.A. and Fatigue was also found (R=-,384, P&lt;,01). <h3>Conclusion</h3> The conclusions were that the patients with SLE in Greece do not perform high level of P.A. and exercise. The moderate level of P.A. was more likely activities of day living, that are classed as P.A., than exercise. Furthermore, the sample choose a sedentary lifestyle, although correlation between P.A. and QoL and Fatigue in patients with S.L.E. was found. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1624 MUSCULOSKELETAL PROBLEMS IN YOUNG DOCTORS
Authors: I. Sellami, A. Feki, M. A. Ghrab, M. Hajjaji, K. Jmal Hammami, S. Baklouti, M. L. Masmoudi
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Musculoskeletal problems (MSP) represent a major problem in the general population and also in occupational settings. Young interns and residents in medicine are exposed to different types of physical constraints (e.g., working long hours, lifting and carrying heavy objects, repetitive movements, etc.), which may lead to musculoskeletal disorders. <h3>Objectives</h3> Evaluate MSP in interns and residents working in the University Hospitals of Sfax, Tunisia. <h3>Methods</h3> We conducted a study during the month of January 2023 using the Nordic questionnaire to screen MSPs. The questionnaire was self-administrated and evaluated along with MSPs on the sociodemographic characteristics and perceived work strain measured with the borg scale. <h3>Results</h3> Our population consisted of 147 interns and residents. The sex ratio was 0.48 and the mean age was 25.41±2.12. Most participants were interns and 1st-year residents (53.7% and 19.7% respectively). Smokers represented 5.4% of the total population. The mean Body Mass index was 22.77± 3.7 and 20.8 % of the population presented as overweight or obese. Among the participants, 6.1% had priors of MSPs. Sixty young doctors (40.8%) reported practising a regular leisure activity with a mean of 3.76+-2.99 hours per week. The physical strain was 6.75± 2.32. Fifty-eight individuals (39.5%) reported having MSPs in the past year and twenty-four (16.3%) during the past week. Neck pain was the most frequent complaint (37.9%) in the past year followed by back pain (24.13% for the upper back and 22.4% for the lower back). The higher perceived physical strain was associated with more frequent musculoskeletal problems during the previous week (p&lt;0.01) and priors of MSP were associated with more frequent complaints in the previous year(p&lt;0.01). BMI was not associated with the presence of MSPs. Smoking tobacco seemed to be a protective factor against neck pain (p=0.016). <h3>Conclusion</h3> Exposure to musculoskeletal constraints is frequent in interns and residents and is often underdiagnosed. More attention is needed for this young population to prevent them from developing chronic MSDs in the future. <h3>References</h3> NA. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
POS1604 IL-13 INHIBITION USED FOR ATOPIC DISEASES IS ASSOCIATED WITH RISK OF PSORIATIC ARTHRITIS
Authors: S. S. Zhao, K. Hyrich, Z. Yiu, A. Barton, J. Bowes
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Inhibitors of the IL-13 pathway, such as dupilumab and tralokinumab, are licensed to treat atopic diseases such as eczema and asthma. Musculoskeletal adverse events that resemble enthesitis and psoriatic arthritis (PsA) after dupilumab initiation have been reported, but evidence is limited to case reports and spontaneous pharmacovigilance with uncertain causal inference. Naturally occurring genetic variation in drug targets can provide insight into their potential adverse effects. <h3>Objectives</h3> To investigate whether genetically proxied IL-13 inhibition (IL-13i) increases risk of PsA and other spondyloarthritis-related diseases. <h3>Methods</h3> Dupilumab is recognised to reduce eosinophil count in clinical studies; we therefore used it as the biomarker of IL-13i. We instrumented IL-13i using missense (protein coding) variants within the <i>IL13</i> gene that are associated with circulating eosinophil count at genome-wide significance (p&lt;5x10<sup>-8</sup>) in a study of 563,946 individuals. Outcome genetic associations were taken from studies of PsA, psoriasis, Crohn's disease, ulcerative colitis, ankylosing spondylitis and iritis. To examine instrument validity, we used atopic eczema and asthma as positive control outcomes, and rheumatoid arthritis as a negative control. We used the ratio method, with estimates scaled to per standard deviation (SD ~0.14x10<sup>9</sup>/L) reduction in eosinophil count. <h3>Results</h3> One missense variant, rs20541, was selected to proxy IL-13i. Genetically proxied IL-13i was associated with increased risk of PsA (OR 37.39; 95%CI 11.52, 121.34), psoriasis (OR 20.08; 4.38, 92.01), Crohn's disease (OR 3.49; 1.38, 8.81), but not ulcerative colitis, ankylosing spondylitis or iritis. IL-13i was associated with reduced risk of positive control outcomes, but not with the negative control (Table 1). <h3>Conclusion</h3> Genetically proxied IL-13 inhibition is associated with increased risk of PsA, psoriasis and Crohn's disease, which may be a class effect relevant to other IL-13i that are not yet reported to have Th17-type adverse events. These findings are compatible with the hypothesis that Th2 cytokines IL-4/-13 may act as a restraint toward Th17-type disease activation in some organs. Clinicians assessing adverse events after dupilumab initiation should be aware of incident PsA and related features. This study demonstrates the value of genetic instrumental variable analyses in evaluating rare adverse events in the study of drug safety. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.